PL05.03: Radio-Oncology

Abstract

When I commenced training in radiation oncology in 1973, there were no CT scanners, calculations were done with slide rules, and chemotherapy, let alone combined modality therapy, had no established role in the treatment of non-small cell lung cancer. An influential trial published in the Lancet in 19711 had shown no difference in survival whether patients were randomized to radiotherapy, chemotherapy, a combination of the two or a policy of wait-and–see. Yet within 30 years, the standard of care for patients with inoperable lung cancer being treated for cure, both small cell and non-small cell, had, ironically, become, and remains, concomitant chemotherapy and radiotherapy. The outlook for patients generally regarded as incurable at the outset of my career is that up to one in three selected patients can now expect to live five years as a result of chemoradiation. Patients with stage I non-small cell lung cancer can have their cancer successfully ablated by non-invasive stereotactic radiotherapy in 90% of cases. The developments which led to these changes can be grouped according to three main themes: the impact of the computer revolution; a better understanding of the natural history and biology of the disease, and the introduction of mutimodality therapy. Better identification and delineation of the tumor are critical to the success of radiotherapy, in particular avoidance of the catastrophic “geographic miss.” Without computers, the CT and hybrid PET/CT scanners could not have been possible. These dramatically improved the accuracy of staging as well as providing 3D information on the relationship of the soft tissue target to the nearby dose-limiting organs at risk. As computing power increased it became possible to create 4D images of moving tumors, and to image the target with on-board CT scanners attached to the linac immediately before treatment, so making image guided stereotactic ablative radiotherapy possible. Powerful computerized treatment planning systems are now able to create complex dose distributions conforming to the irregularities of any target volume, and to provide dose-volume metrics predictive of risks of normal tissue damage. The recognition that the central nervous system is a sanctuary site which can harbor metastatic disease leading to treatment failure in spite of successful chemotherapeutic eradication of extracranial disease, particularly in small cell lung cancer, led to the introduction of prophylactic cranial irradiation. The British study of continuous hyperfractionated accelerated radiotherapy (CHART) which was given over 12 days to patients with inoperable non-small cell lung cancer resulted in better survival than treatment given over six weeks, even though the total dose was lower. This trial provided clinical support for the notion of treatment induced accelerated repopulation, and reinforced the principle that total treatment times should be kept short in both small cell and non-small cell lung cancer, both when radiotherapy is used alone, and when in combination with chemotherapy. The limitations of single modality therapy for a disease with a high propensity for developing genetically determined resistance have long been recognized, and have stimulated the development of strategies simultaneously employing non-cross resistant therapies to maximize tumor cell kill, in line with the principles espoused by Goldie and Coldman.2 The use of concomitant platinum based chemotherapy with high dose radiotherapy is now well established by meta-analysis as improving survival of both non-small cell and small cell lung cancers, but it is also more toxic. Amelioration of these toxicities represents a major challenge for the future. It is likely that the technical progress in radiation treatment planning and delivery is close to a plateau, and that future progress will depend more on understanding the biology of the disease and its response, and that of the normal tissues, to radiation damage. Biomarkers of response and toxicity, so spectacularly harnessed to advantage by our medical oncology colleagues, are desperately needed to tailor the radiotherapy prescription to the needs of each individual and their cancer. Finally, it is evident that in many jurisdictions, including industrialized wealthy nations, that many patients are either receiving substandard radiotherapy that might increase their chances of cure, or are not receiving treatment at all.3 Unless these problems can be addressed, the benefits of the remarkable advances in technology and biology documented above will shamefully be restricted to only a fraction of those afflicted with locoregional disease. 1. Durrant KR, Berry RJ, Ellis F, Ridehalgh FR, Black JM, Hamilton WS. Comparison of treatment policies in inoperable bronchial carcinoma. Lancet. 1971;1(7702):715-9. 2. Goldie JH, Coldman AJ, Gudauskas GA. Rationale for the use of alternating non-cross-resistant chemotherapy. Cancer Treat Rep. 1982;66(3):439-49. 3. Vinod SK. International patterns of radiotherapy practice for non-small cell lung cancer. Semin Radiat Oncol. 2015;25(2):143-50. lung cancer, radiation oncology, history